40 Participants Needed

ADCLEC.syn1 CAR T-Cell Therapy for Acute Myeloid Leukemia

Recruiting at 6 trial locations
JP
MG
Overseen ByMark Geyer, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test the safety of ADCLEC.syn1 CAR T cells in people with relapsed or refractory AML. The researchers will try to find the highest dose of ADCLEC.syn1 CAR T cells that causes few or mild side effects in participants. Once the researchers find this dose, it will test it in a new group of participants to see if it is effective in treating their relapsed/refractory AML.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before participation. Steroids above a certain dose must be stopped 7 days before a procedure, and chemotherapy should be stopped one week prior. Hydroxyurea can be used up to 72 hours before certain procedures.

What data supports the effectiveness of the ADCLEC.syn1 CAR T-Cell Therapy treatment for Acute Myeloid Leukemia?

Research shows that CAR T-cell therapy, like ADCLEC.syn1, has been successful in treating certain blood cancers by targeting specific cancer cells. Studies suggest that ADCLEC.syn1 can effectively target leukemia cells while minimizing harm to normal cells, showing promise in treating acute myeloid leukemia.12345

Is ADCLEC.syn1 CAR T-Cell Therapy safe for humans?

ADCLEC.syn1 CAR T-Cell Therapy has shown potential in targeting acute myeloid leukemia (AML) while minimizing harm to normal cells. However, like other CAR T-cell therapies, it may cause side effects such as myeloablation (reduction of bone marrow activity) and cytokine release syndrome (a severe immune reaction).24678

How is ADCLEC.syn1 CAR T-Cell Therapy different from other treatments for acute myeloid leukemia?

ADCLEC.syn1 CAR T-Cell Therapy is unique because it targets two specific markers (ADGRE2 and CLEC12A) on leukemia cells, which helps to selectively attack cancer cells while sparing normal cells. This dual targeting approach reduces the risk of damaging healthy blood-forming cells, a common issue with other CAR T-cell therapies for acute myeloid leukemia.2491011

Research Team

Jae Park, MD - MSK Leukemia Specialist ...

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with relapsed or refractory Acute Myeloid Leukemia (AML) who are in good physical condition (ECOG 0-1), have a suitable stem cell donor, and functioning major organs can join this trial. Those with acute promyelocytic leukemia, certain infections like HBV/HCV, other active cancers needing treatment, recent heart issues, uncontrolled infections or previous CAR therapy cannot participate.

Inclusion Criteria

My kidney and liver functions are within the required limits.
I have a matching donor for a stem cell transplant.
I am fully active or can carry out light work.
See 3 more

Exclusion Criteria

I have not taken clofarabine or cladribine in the last 3 months.
I have been diagnosed with acute promyelocytic leukemia.
I have brain-related symptoms or confirmed brain disease.
See 10 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Chemotherapy

Participants receive conditioning chemotherapy prior to CAR T cell infusion

1 week
Inpatient or outpatient

Treatment

Participants receive ADCLEC.syn1 CAR T cell infusions with dose escalation to determine the maximum tolerated dose

2-7 days post-chemotherapy
Inpatient

Dose Expansion

Selected dose levels are tested in additional patients to determine the recommended phase 2 dose (RP2D)

Variable, up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • ADCLEC.syn1 CAR T cells
  • Conditioning chemotherapy
Trial OverviewThe study is testing the safety of ADCLEC.syn1 CAR T cells along with conditioning chemotherapy in AML patients. It aims to find the highest dose that's safe with few side effects and then test its effectiveness against AML that has come back or hasn't responded to other treatments.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: ADCLEC.syn1 CAR T cellsExperimental Treatment2 Interventions
The dose escalation cohort size of 3 patients in each cohort will be infused with escalating doses of ADCLEC.syn1 CAR T cells to inform the RP2D. There are 4 planned flat-dose levels: 25 × 10\^6, 75 × 10\^6 , 225 × 10\^6 , and 450 × 10\^6 CAR T cells and 1 de-escalation dose: 10 × 10\^6 CAR T cells. After dose escalation, one or two dose levels will be selected for dose expansion cohort(s).Two to 7 days following completion of the conditioning chemotherapy, the frozen CAR T cells will be thawed and administered. Conditioning chemotherapy may occur either outpatient or inpatient, and T cell infusions will occur as inpatient. Up to approximately 12 additional patients each if two doses are selected or approximately 16 additional patients, if one dose is selected, will be treated in the dose expansion phase to determine RP2D.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials
1,998
Recruited
602,000+

Takeda

Industry Sponsor

Trials
1,255
Recruited
4,219,000+
Dr. Naoyoshi Hirota profile image

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber profile image

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Findings from Research

CAR T-cell therapy has the potential to improve outcomes for patients with acute myeloid leukemia (AML) by specifically targeting leukemia cells, but there are significant challenges to its effectiveness and safety.
Strategies being explored to enhance CAR T-cell therapy in AML include targeting specific leukemia antigens to reduce side effects, using checkpoint inhibitors to counteract immune suppression caused by leukemia, and developing allogenic CAR T cells to make the treatment more accessible to patients.
Prospect of CAR T-cell therapy in acute myeloid leukemia.Badar, T., Manna, A., Gadd, ME., et al.[2022]
Relapse after conventional chemotherapy is a significant issue in patients with acute myeloid leukemia (AML), and the only potentially curative treatment is allogeneic hematopoietic stem cell transplantation (allo-HSCT), which can eliminate residual leukemia cells but still faces challenges with relapse.
Current efforts are focused on adapting CD19-targeted CAR T cell therapy, which has been successful in B-cell malignancies, for myeloid malignancies, but the lack of specific antigens on myeloid cells poses a risk of damaging normal blood stem cells, making it crucial to develop safe genetic modifications and strategies for effective treatment.
CAR T Cells for Acute Myeloid Leukemia: State of the Art and Future Directions.Mardiana, S., Gill, S.[2023]
Current treatments for acute myeloid leukemia (AML) often fail or lead to relapses, highlighting the need for new therapeutic strategies.
Chimeric antigen receptor (CAR) T cell therapy, which has shown success in treating B-lineage cancers, is being explored for AML, with ongoing research into potential surface markers and strategies to improve its effectiveness in this type of leukemia.
Chimeric antigen receptors for adoptive T cell therapy in acute myeloid leukemia.Fan, M., Li, M., Gao, L., et al.[2021]

References

Prospect of CAR T-cell therapy in acute myeloid leukemia. [2022]
CAR T Cells for Acute Myeloid Leukemia: State of the Art and Future Directions. [2023]
Chimeric antigen receptors for adoptive T cell therapy in acute myeloid leukemia. [2021]
Cooperative CAR targeting to selectively eliminate AML and minimize escape. [2023]
Current challenges for CAR T-cell therapy of acute myeloid leukemia. [2020]
How close are we to CAR T-cell therapy for AML? [2021]
Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. [2021]
Chimeric Antigen Receptor T Cells in Acute Myeloid Leukemia. [2023]
CD70 CAR T cells in AML: Form follows function. [2022]
Combinatorial antigen targeting strategies for acute leukemia: application in myeloid malignancy. [2023]
Adapter CAR T cells to counteract T-cell exhaustion and enable flexible targeting in AML. [2023]